EAGER: Elucidating the basis of retrotransposon target preference

佩内洛普类元素的转位机制是真核生物中最后一个尚未确定的可溯性机制之一。建立一个易于处理的系统来剖析这些元素的机制和目标偏好，不仅可以促进我们对自然发生的基因组重排的基本理解，而且可能有助于在真核生物中设计新的基因传递系统。该项目将支持一名本科生暑期实习，在MBL密集的暑期研究氛围中培养一名学生的微生物学和分子生物学技术。逆转录转座子是可移动的遗传元件，即插入多细胞生物基因组中的DNA片段，但可以利用类似病毒的机制自主复制RNA，然后对其进行逆转录。两个主要的反转录转座子亚类是ltr和非ltr （LINE）反转录转座子，第三个主要亚类，称为penelope样元件，最近才被发现，并没有得到很好的研究。有趣的是，与其他两类反转录转座子不同，penelope样元件似乎位于核苷酸序列排列成所谓的（TA）n微卫星的基因组区域，即两个核苷酸的多次重复。在活跃的蛋白质编码基因中很少发现这样的重复，在这个项目中，研究人员正在试图定义逆转录因子如何“找到”整合的分子细节。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Transposition mechanisms of Penelope-like elements are one of the last uncharacterized mechanism of retromobility in eukaryotes. Establishment of a tractable system to dissect the mechanism and target preferences of these elements would not only advance our basic understanding of naturally occurring genome rearrangements but may also help design novel gene delivery systems in eukaryotes. The project will provide support for a summer undergraduate internship to train a student in microbiology and molecular biology techniques in the context of intensive summer research atmosphere at the MBL.Retrotransposons are mobile genetic elements, i.e., fragments of DNA that are inserted in the genomes of multicellular organisms, but may replicate autonomously, using virus-like mechanisms of making RNA and then reverse transcribing it. The two main retrotransposon subclasse are the LTR-and non-LTR (LINE) retrotransposons and the third major subclass, named Penelope-like elements has been found only recently and is not well-studied. Interestingly, and unlike the other two classes of retrotransposons, Penelope-like elements appear to locate in those regions of the genome where the nucleotide sequence is arranged into the so-called (TA)n microsatellites, i.e., multiple repetitions of just two nucleotides. Such repetitions are rarely found within active protein-coding genes, and in this project, researchers are seeking to define the molecular details of how the retroelements 'find' where to integrate.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.